Ziana Gel

SIDE EFFECTS

Clinical Studies Experience

Because clinical trials are conducted under prescribed conditions, adverse
reaction rates observed in the clinical trial may not reflect the rates observed
in practice. The adverse reaction information from clinical trials does, however,
provide a basis for identifying the adverse reactions that appear to be related
to drug use for approximating rates.

The safety data presented in Table 1 (below) reflects exposure to ZIANA Gel (clindamycin phosphate, tretinoin)
in 1,853 patients with acne vulgaris. Patients were 12 years and older and were
treated once daily for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with ZIANA Gel (clindamycin phosphate, tretinoin) were compared to adverse reactions in
patients treated with clindamycin phosphate 1.2% in vehicle gel, tretinoin 0.025%
in vehicle gel, and the vehicle gel alone:

At each study visit, application site reactions on a scale of 0 (none), 1 (mild),
2 (moderate), and 3 (severe), and the mean scores were calculated for each of
the local skin reactions. In Studies 1 and 2, 1277 subjects enrolled with moderate
to severe acne, 854 subjects treated with ZIANA Gel (clindamycin phosphate, tretinoin) and 423 treated with vehicle.
Analysis over the twelve week period demonstrated that cutaneous irritation
scores for erythema, scaling, itching, burning, and stinging peaked at two weeks
of therapy, and were slightly higher for the ZIANA-treated group, decreasing
thereafter.

One open-label 12-month safety study for ZIANA Gel (clindamycin phosphate, tretinoin) showed a similar adverse
reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.

DRUG INTERACTIONS

Concomitant Topical Medication

Concomitant topical medication, medicated or abrasive soaps and cleansers,
soaps and cosmetics that have a strong drying effect, and products with high
concentrations of alcohol, astringents, spices or lime should be used with caution.
When used with ZIANA Gel (clindamycin phosphate, tretinoin) , there may be increased skin irritation.

Erythromycin

ZIANA Gel (clindamycin phosphate, tretinoin) should not be used in combination with erythromycin-containing products
due to its clindamycin component. In vitro studies have shown antagonism
between these two antimicrobials. The clinical significance of this in vitro
antagonism is not known.

Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may
enhance the action of other neuromuscular blocking agents. Therefore, ZIANA Gel (clindamycin phosphate, tretinoin) should be used with caution in patients receiving such agents.